This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human CD38 is a membrane protein involved in versatile antigenic and physiological functions. On the cell membrane of leukocytes, this protein is very flexible and can interact with other cell surface molecules to elicit signal events resulting in cell proliferation, differentiation, and programmed cell death. Besides, human CD38 is an ectoenzyme and can synthesize and hydrolyze a cyclic nucleotide capable of mobilizing calcium ions. The crystal structure of human CD38 extracellular domain has been determined. However, it is structurally unknown how this enzyme communicates with other cellular molecules towards signaling. In this study, we propose to use high pressure as an external force to tantalize the protein in its crystalline state. By exploring a series of pressure (from 1 atmosphere to ~10,000 atmosphere) on CD38 crystals, we expect to characterize the dynamic behavior of the protein's structural plasticity/flexibility. Besides, we also expect to use this external force as a tool to mechanistically probe biological reactions that otherwise evade from investigation.